ERBB2

Also known as CD340, HER-2/neu, HER2, NEU

Tumour types

breast cancer, gastric cancer, gastroesophageal junction adenocarcinoma

ERBB2 (also known as HER2) encodes a receptor tyrosine-protein kinase of the EGFR/ErbB family. Amplification or overexpression drives a subset of breast and gastric/gastroesophageal cancers.

The clinically actionable alteration is typically gene amplification (assessed by ISH) or protein overexpression (assessed by IHC, scored 0/1+/2+/3+), rather than a specific point mutation.

Clinical significance

HER2-positive status (IHC 3+, or IHC 2+ with ISH amplification) identifies patients eligible for HER2-targeted therapy in breast and gastric/GEJ adenocarcinoma.
fda — FDA-approved product labeling for HER2-targeted agents
HER2 status can change between primary and metastatic disease, so re-testing at relapse or progression is recommended before selecting HER2-targeted therapy.
pmc — PMC Open Access Subset, oncology literature

FDA-approved treatments

Perjeta (pertuzumab) — HER2-positive breast cancer, in combination with trastuzumab and chemotherapy (neoadjuvant, adjuvant, and metastatic settings) [ema]
Herceptin (trastuzumab) — HER2-positive breast cancer and HER2-positive metastatic gastric/gastroesophageal junction adenocarcinoma [fda]
Enhertu (trastuzumab deruxtecan) — HER2-positive and HER2-low unresectable or metastatic breast cancer, and other HER2-expressing solid tumors [fda]
Tukysa (tucatinib) — HER2-positive metastatic breast cancer, including patients with brain metastases, in combination with trastuzumab and capecitabine [fda]

Prevalence

HER2 is overexpressed or amplified in approximately 15%-20% of breast cancers and approximately 15%-20% of gastric/gastroesophageal junction adenocarcinomas. [fda]

Tests / detection method

IHC, ISH/FISH, NGS (amplification calling)

Therapeutic pipeline

Bispecific HER2-targeted antibodies [fda]
Next-generation HER2-directed antibody-drug conjugates (HER2-ultralow expression) [fda]

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